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Chun-Lin Kuo,1 Shu-Man Hsieh Li,*,2 Shu-Yi Liang,*,2 Shu-Ting Liu,2 Li-Chun Huang,2 Wei-Ming Wang,3 Li-Chen Yen,2,4 Shih-Ming Huang21Department of Orthopaedic Surgery, Tri-Service General Hospital, National Defense Medical Center, Taiwan, Republic of China; 2Department of Biochemistry, National Defense Medical Center, Taiwan, Republic of China; 3Department of Dermatology, Tri-Service General Hospital, National Defense Medical Center, Taiwan, Republic of China; 4Department of Microbiology and Immunology, National Defense Medical Center, Taiwan, Republic of China*These authors contributed equally to this workBackground: Differentiated embryo chondrocyte 1 (DEC1) is a helix-loop-helix transcription factor that directly binds to the class B E-box in target genes. DEC1 exerts both pro-survival and pro-apoptotic effects in a cell- and tissue-dependent manner. Its actions play role the progression of cancer remains unclear.Methods: We first examined the functional roles of DEC1 using the transient promoter reporter assay. Then, the knockdown of DEC1 expression was performed with the short hairpin RNA strategy in HeLa and A2058 cancer cell lines to check the cell cycle and mitochondrial function profile using the flow cytometry and Seahorse assays. We later clarified the role of DEC1 in the tumorigenesis using the colony formation, anchorage-independent growth assay, and cellular proliferation analysis.Results: In the present study, we tested two guanide-containing drugs, metformin and phenformin, and found that both exhibit cytotoxicity against HeLa cervical carcinoma and A2058 melanoma cells. This effect was mediated, at least in part, through activation of the AMPK pathway; degradation of important cellular proteins, such as DEC1 and p53; and suppression of mitochondrial function, colony formation, and anchorage-independent cell proliferation. Our results further suggest that the cytotoxicity of metformin and phenformin reflect the impact of the repressive actions of DEC1 on gene expression, including DEC1 itself. This in turn suppresses both anchorage-independent growth and cell proliferation.Conclusion: These findings provide several lines of evidence suggesting that DEC1 activity contributes to tumorigenicity and that the antitumor properties of biguanides reflect their ability to inhibit DEC1 functions.Keywords: differentiated embryo chondrocyte 1, p53, metformin, phenformin, tumorigenesis

Wen-Jiun Chou,1 Liang-Jen Wang,1 Chien-Ho Lin,2 Sun-Yuan Liang,3 Vincent Chin-Hung Chen,4 Yuh-Ming Hou,5 Rong-Rong Huang,6 Miao-Chun Chou,1 Chi-Yung Shang,7 Chi-Pui Ho,6 Meng-Chuan Lai8 1Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 2Department of Psychiatry, Chimei Medical Center, Tainan, 3Department of Psychiatry, Changhua Hospital, Changhua, 4Department of Psychiatry, Chang Gung Memorial Hospital and University, 5Chia-Yi Christian Hospital, Chiayi, 6Department of Child and Adolescent Psychiatry, Kai-Suan Psychiatric Hospital, Kaohsiung, 7Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; 8Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK Purpose: This prospective, single-arm, open-label, 8-week, multicenter study investigated the effectiveness of switching from immediate-release methylphenidate (IR-MPH) to osmotic controlled-release methylphenidate (OROS-MPH) in patients with attention-deficit/hyperactivity disorder (ADHD).Patients and methods: Overall, 296 patients with ADHD (mean age: 9.5 years) already on IR-MPH treatment were enrolled. Upon enrollment, a flexible dose of OROS-MPH was administered, replacing IR-MPH. Patients were assessed at baseline and weeks 2, 4, and 8 using the Swanson, Nolan, and Pelham version IV scale (SNAP-IV) and the Clinical Global Impression for ADHD symptoms. The Social Adjustment Inventory for Children and Adolescents assessed social functions, and the Chinese Health Questionnaire (CHQ) and Family Adaptation, Partnership, Growth, Affection, and Resolve evaluated parental and family functions.Results: Switching from IR-MPH to OROS-MPH yielded significant improvements in all ADHD symptoms, as rated by parents, teachers (SNAP-IV), and study investigators (Clinical Global Impression). CHQ scores and all Social Adjustment Inventory for Children and Adolescents subscores except spare time scores improved significantly. Patients with poor IR-MPH adherence had greater improvements in teacher-rated SNAP-IV and mothers’ mental health (CHQ) after switching. Conclusion: Switching from IR-MPH to OROS-MPH improved patients’ behavioral ADHD symptoms and social adjustment, and mental health of patients’ mothers. This was most evident in patients who previously exhibited poor IR-MPH adherence. Keywords: ADHD, central nervous system stimulant, drug adherence, family, social adjustment

Shuyan Liang,* Jun Hu,* Yuanyuan Xie, Qing Zhou, Yanhong Zhu, Xiangliang Yang National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: Cancer immunotherapy based on nanodelivery systems has shown potential for treatment of various malignancies, owing to the benefits of tumor targeting of nanoparticles. However, induction of a potent T-cell immune response against tumors still remains a challenge. In this study, polyethylenimine-modified carboxyl-styrene/acrylamide (PS) copolymer nanospheres were developed as a delivery system of unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides and transforming growth factor-beta (TGF-β) receptor I inhibitors for cancer immunotherapy. TGF-β receptor I inhibitors (LY2157299, LY) were encapsulated to the PS via hydrophobic interaction, while CpG oligodeoxynucleotides were loaded onto the PS through electrostatic interaction. Compared to the control group, tumor inhibition in the PS-LY/CpG group was up to 99.7% without noticeable toxicity. The tumor regression may be attributed to T-cell activation and amplification in mouse models. The results highlight the additive effect of CpG and TGF-β receptor I inhibitors co-delivered in cancer immunotherapy. Keywords: CpG, TGF-β receptor I inhibitor, Pst-AAm copolymer nanosphere, immunotherapy

Shuyan Liang,1 Qing Zhou,1 Min Wang,2,3 Yanhong Zhu,1 Qingzhi Wu,2,3 Xiangliang Yang1 1College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan, People’s Republic of China; 3Biomedical Material and Engineering Center of Hubei Province, Wuhan University of Technology, Wuhan, People’s Republic of China Abstract: Nanoparticles (NPs) are advantageous for the delivery of diagnosis agents to brain tumors. In this study, we attempted to develop an l-cysteine coated FePt (FePt-Cys) NP as MRI/CT imaging contrast agent for the diagnosis of malignant gliomas. FePt-Cys NPs were synthesized through a co-reduction route, which was characterized by transmission electron microscopy, high-resolution transmission electron microscopy, powder X-ray diffraction, Fourier transform infrared spectroscopy, and dynamic light scattering. The MRI and CT imaging ability of FePt-Cys NPs was evaluated using different gliomas cells (C6, SGH44, U251) as the model. Furthermore, the biocompatibility of the as-synthesized FePt-Cys NPs was evaluated using three different cell lines (ECV304, L929, and HEK293) as the model. The results showed that FePt-Cys NPs displayed excellent biocompatibility and good MRI/CT imaging ability, thereby indicating promising potential as a dual MRI/CT contrast agent for the diagnosis of brain malignant gliomas. Keywords: CT, glioma, MRI

Rupa R Patel,1 Stephen Y Liang,1 Pooja Koolwal,2 Frederick Matthew Kuhlmann1 1Division of Infectious Diseases, 2Division of Medical Education, Washington University School of Medicine, St Louis, MO, USA Abstract: Immunocompromised patients are traveling at increasing rates. Physicians caring for these complex patients must be knowledgeable in pretravel consultation and recognize when referral to an infectious disease specialist is warranted. This article outlines disease prevention associated with international travel for adults with human immunodeficiency virus, asplenia, solid organ and hematopoietic transplantation, and other immunosuppressed states. While rates of infection may not differ significantly between healthy and immunocompromised travelers, the latter are at greater risk for severe disease. A thorough assessment of these risks can ensure safe and healthy travel. The travel practitioners’ goal should be to provide comprehensive risk information and recommend appropriate vaccinations or prevention measures tailored to each patient’s condition. In some instances, live vaccines and prophylactic medications may be contraindicated. Keywords: immunocompromised, vaccines, travel, malaria, diarrhea

Goals: Few studies have repeatedly evaluated quality of life and potentially relevant factors in patients with benign primary brain tumor. The purpose of this study was to explore the relationship between the experience of the symptom distress, functional status, depression, and quality of life prior to surgery (T(1)) and 1 month post-discharge (T(2)).Patients and Methods: This was a prospective cohort study including 58 patients with benign primary brain tumor in one teaching hospital in the Taipei area of Taiwan. The research instruments included the M.D. Anderson Symptom Inventory, the Functional Independence Measure scale, the Hospital Depression Scale, and the Functional Assessment of Cancer Therapy-Brain.Results: Symptom distress (T(1): r = -0.90, p < 0.01; T(2): r = -0.52, p < 0.01), functional status (T(1): r = 0.56, p < 0.01), and depression (T(1): r = -0.71, p < 0.01) demonstrated a significant relationship with patients' quality of life. Multivariate analysis identified symptom distress (explained 80.2%, R (inc)(2) = 0.802, p = 0.001) and depression (explained 5.2%, R (inc)(2) = 0.052, p < 0.001) continued to have a significant independent influence on quality of life prior to surgery (T(1)) after controlling for key demographic and medical variables. Furthermore, only symptom distress (explained 27.1%, R (inc)(2) = 0.271, p = 0.001) continued to have a significant independent influence on quality of life at 1 month after discharge (T(2)).Conclusions: The study highlights the potential importance of a patient's symptom distress on quality of life prior to and following surgery. Health professionals should inquire about symptom distress over time. Specific interventions for symptoms may improve the symptom impact on quality of life. Additional studies should evaluate symptom distress on longer-term quality of life of patients with benign brain tumor. [ABSTRACT FROM AUTHOR]

Background: Healthcare fragmentation and lack of care coordination are longstanding problems in cancer care. This study's goal was to provide in-depth understanding of how the organization and fragmentation of healthcare impacts the experiences of patients with advanced cancer and their families, especially near the end-of-life., Methods: This mixed-methods quality improvement study took place at a large multi-specialty healthcare organization in Northern California. Electronic health record data was used to identify patients with advanced cancer and their characteristics. Data were collected 10/2019-05/2022 through periodic patient surveys and in-depth interviews with sampled family members, including open-ended questions about overall healthcare experiences. Data were analyzed using inductive thematic analysis., Results: Overall, 281/482 (58.3%) patients with advanced cancer completed surveys. Surveyed patients' mean age was 68 (SD: 12.8) years, 53% were male, 73% White, 14.2% Asian, 1.4% Black, 3.9% Other; 8.9% Hispanic, and 19.2% were deceased within 12 months. Twenty-four family members completed in-depth interviews: 17/24 (70.8%) were spouses, 62.5% were female and 50% were interviewed after the patient's death. Respondents were generally positive about health care team interactions, but consistently brought up the negative impacts of the organization of healthcare, "It is not the fault of the health care team - it is the way the system works." Three major challenges were identified. (1) Systemic healthcare care fragmentation, including difficulties navigating care across providers and institutions, "It seems like everything is like an isolated incident… there's no overall, big picture viewpoint." (2) Administrative burdens, "In the end I gave up [scheduling care] because I was tired of calling." (3) Financial burdens, "This oncologist wanted to put him on a drug…but it was $4000 a month." Respondents described these challenges leading to worse quality of care, health, and quality of life, and loss of trust in the national healthcare system., Conclusions: These findings illustrate how care fragmentation and administrative and financial burdens lead to worse quality care and distrust of healthcare. Better coordination of patient-centered care, and a fundamental restructuring of a highly fragmented national healthcare system are required to meet the needs of patients with complex conditions like advanced cancer and their families., Competing Interests: Declarations Ethics approval and consent to participate The project was reviewed by the Sutter Health Institutional Review Board and was determined not to be human subjects research, so formal signed consent was not required. We provided participants with an informed written or verbal description of the study and how data would be used before they agreed to participate. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background and Aims: Adenoma detection rate (ADR) is a key quality metric in colonoscopy, reflecting the ability to detect adenomas. However, concerns remain regarding the robustness of ADR as a benchmark. In particular, "one and done" phenomenon may exists where physicians are less motivated to find additional adenoma following the first adenoma. To investigate this further, we aim to understand the relationship between single and multiple adenoma detection., Methods: We conducted a retrospective cohort study using data from 89,587 screening colonoscopies performed by 32 endoscopists within the Sutter Health-Palo Alto Medical Foundation between 2015 and 2020. We analyzed ADR, single adenoma detection rate (ADR1), and multiple adenoma detection rate (ADR2+) using multivariate logistic regression and linear regression models. Endoscopists were then fit into 4 categories based on median ADR1 and ADR2+ (low ADR1, high ADR2+ ["all or none"], low ADR1, low ADR2+ ["none and done"], high ADR1, high ADR2+ ["all and done"], high ADR1, low ADR2+ ["one and done"]., Results: The overall ADR was 45.4%. ADR, ADR1, and ADR2+ were significantly associated with similar factors including older age, male sex, higher body mass index, smoking status, high-risk colonoscopies, Medicare insured, use of mucosal assist devices, longer withdrawal times, adequate preparation, and procedures performed by female, high-volume endoscopists with a longer duration in practice. The median ADR1 and ADR2+ were 23.95% and 21.29%, respectively. ADR1 and ADR2+ were positively correlated (Pearson correlation coefficient (r), 0.701, p<0.001). Only 4 of 32 endoscopists fit our "one and done" category., Conclusion: Our findings suggest that ADR1 correlates with ADR2+. Despite concerns, the "one and done" phenomenon is not commonly seen in clinical practice. ADR remains a good surrogate marker for multiple adenoma detection., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Novel C18-functionalized magnetic nanomaterials; i.e., C18@poly-styrene-divinylbenzene-glycidyl methacrylate-Fe3O4 (C18@PS-DVB-GMA-Fe3O4) have been synthesized by using N, N-dimethyloctadecylamine as modifying agent, which could be beneficial to remove the blood phospholipids. The C18@PS-DVB-GMA-Fe3O4 nanoparticles have been used and evaluated in the Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) procedure for human plasma prior to the analysis of propofol by supercritical fluid chromatography (SFC). In the QuEChERS procedure, human plasma samples are directly mixed with extraction solvent and C18@PS-DVB-GMA-Fe3O4 nanoparticles, and the extraction and cleanup procedures have been accomplished simultaneously. The SFC separation was performed with a C18 column (Thermo Scientific™ Acclaim™ 120, 250 × 4. 6 mm, 5 μm) within 5 min, using thymol as the internal standard. Supercritical carbon dioxide was used as the mobile phase with methanol as the cosolvent at the flow rate of 1.0 mL/min. The column temperature was 38°C, and detection wavelength was 275 nm. A good linearity was obtained among the propofol concentration range of 0.5-10 mg/L (R2 = 0.9997) with the limit of detection of 0.17 mg/L. Recoveries were in the range of 76.5-91.9%, with RSD less than 7.9%. These results suggested that method is convenient, rapid with high accuracy and little matrix effect, and suitable for rapid determination of propofol plasma concentration., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Sphenoid sinus mucocele (SSM) represents a relatively rare disease among pediatric population as compared to adults, with a 1% to 3% incidence of all paranasal sinus mucoceles. Since the initial symptoms varied often, SSM caused blindness was scarcely seen. Case Presentation: Here we described an unusual case of small, isolated SSM causing acute visual loss in a 9-year-old girl. The patient first consulted an ophthalmologist for her right blindness. A diagnosis of SSM was suspected indicated by an orbital MRI scan. Thereafter the patient was referred to our department and an endoscopic sphenoidotomy and optic nerve decompression was performed. Surprisingly, her vision was relieved immediately after surgery, followed by dramatic improvement during the postoperative 20-month follow-up period. Conclusion: To our knowledge, a better understanding of SSM in pediatrics is essential for clinicians, including neurologists, ophthalmologists, and otolaryngologists to make early diagnoses and correct treatment by MRI and CT scan. Prompt surgical intervention of endoscopic transnasal sphenoidectomy is a quite safe, effective, and minimally invasive method for patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Candida auris is an emerging pathogen and human health threat. However, diagnosis and treatment of fungal infection due to C. auris are challenging., Objective: This narrative review provides a focused overview of C. auris for the emergency clinician., Discussion: C. auris was first identified in 2009 and is currently present on all continents except Antarctica. C. auris possesses multiple genetic factors resulting in antimicrobial resistance, increased virulence and survival within the host, and environmental adaptation. It is readily transmitted from person to person and from the environment to a person, resulting in colonization. Infection may develop days to months following colonization, most commonly in those with immunocompromised state, significant comorbidities or other underlying conditions, healthcare exposure, and recent antimicrobial therapy. Candidemia, device infection (e.g., central venous catheter), soft tissue or wound infection, burn infection, osteomyelitis, myocarditis, meningitis, and urinary tract infection have been associated with C. auris. Samples should be obtained from the suspected site of infection for microbiological culture. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with reference databases to differentiate C. auris from other species is optimal for diagnosis, though other molecular testing methods are available. Treatment is challenging due to antifungal resistance, with over 90% resistant to fluconazole. Echinocandins are most commonly used as the first line therapy. Prevention of colonization and infection are vital and include screening in high-risk populations and strict adherence to infection prevention practices with contact precautions and hand hygiene, as well as appropriate decontamination of patient areas., Conclusion: An understanding of C. auris can assist emergency clinicians in the care of infected or colonized patients., Competing Interests: Declaration of competing interest None. No authors have published a similar topic on Candida auris. No author is submitting a manuscript on this subject to another journal until AJEM makes a decision to reject or actually publishes (not just accepts) this submission. No AI program was used in the construction of this manuscript., (Published by Elsevier Inc.)

Overexpression of Dunaliella parva (D. parva) malic enzyme (ME) gene (DpME) significantly increased DpME expression and ME enzyme activity in transgenic D. parva. Nitrogen limitation had an inhibitory effect on protein content, and DpME overexpression could improve protein content. Nitrogen limitation increased carbohydrate content, and Dunaliella parva overexpressing malic enzyme gene under nitrogen limitation (DpME-N - ) group showed the lowest starch content among all groups. Dunaliella parva overexpressing malic enzyme gene under nitrogen sufficient condition (DpME) and DpME-N - groups showed considerably high mRNA levels of DpME. ME activity was significantly enhanced by DpME overexpression, and nitrogen limitation caused a smaller increase. DpME overexpression and nitrogen limitation obviously enhanced lipid accumulation, and DpME overexpression had more obvious effect. Compared with control (wild type), lipid content (68.97%) obviously increased in DpME-N - group. This study indicated that the combination of DpME overexpression and nitrogen limitation was favorable to the production of microalgae biodiesel., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: This study compared Lynch syndrome universal tumor screening (UTS) across multiple health systems (some of which had 2 or more distinct UTS programs) to understand multilevel factors that may affect the successful implementation of complex programs., Methods: Data from 66 stakeholder interviews were used to conduct multivalue coincidence analysis and identify key factors that consistently make a difference in whether UTS programs were implemented and optimized at the system level., Results: The selected coincidence analysis model revealed combinations of conditions that distinguish 4 optimized UTS programs, 10 nonoptimized programs, and 4 systems with no program. Fully optimized UTS programs had both a maintenance champion and a positive inner setting. Two independent paths were unique to nonoptimized programs: (1) positive attitudes and a mixed inner setting or (2) limited planning and engaging among stakeholders. Negative views about UTS evidence or lack of knowledge about UTS led to a lack of planning and engaging, which subsequently prevented program implementation., Conclusion: The model improved our understanding of program implementation in health care systems and informed the creation of a toolkit to guide UTS implementation, optimization, and changes. Our findings and toolkit may serve as a use case to increase the successful implementation of other complex precision health programs., Competing Interests: Conflict of Interest No competing financial interests are reported by any authors in relation to the work described in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/objectives: Brain tumor patients confront numerous challenges arising from diagnosis and treatment, and these impact the patient's physical, mental, and social functions at all levels. Primary informal caregivers assume a pivotal role in home-based patient care. Of particular importance are the coping strategies employed by family caregivers, as they can influence both their own health and the overall quality of home care. This study aimed to explore the associations among family function, caregiving competence, and coping strategies among primary informal caregivers., Methods: This study adopted a cross-sectional correlational design and convenience sampling to survey the primary informal caregivers of 111 brain tumor patients. The study instruments included the Family Assessment Device General Function, Caregiving Competence Scale, and Revised Ways of Coping Checklist., Results: The findings of this study revealed a significant positive correlation between the family function of primary informal caregivers and their employment of emotion-focused coping (r = 0.209, p < 0.05). Furthermore, caregiving competence exhibited a positive association with problem-focused coping (r = 0.242, p < 0.05) and emerged as a significant predictor of problem-focused coping (β = 0.182, p < 0.05). However, neither family function (r = 0.059, p < 0.05) nor caregiving competence (r = 0.031, p < 0.05) demonstrated significant associations with total coping strategies., Conclusions: The findings of this study affirmed that enhancing the caregiving competence of primary informal caregivers of brain tumor patients can facilitate the adoption of problem-focused coping strategies.

Background: Recent therapeutic advances have improved survival among lung cancer (LC) patients, who are now at high risk of second primary lung cancer (SPLC). Hispanics comprise the largest minority in the United States, who have shown a lower LC incidence and mortality than other races, and yet their SPLC risk is poorly understood. We quantified the SPLC incidence patterns among Hispanics vs other races., Methods: We used data from the Multiethnic Cohort, a population-based cohort of 5 races (African American, Japanese American, Hispanic, Native Hawaiian, and White), recruited between 1993 and 1996 and followed through 2017. We identified patients diagnosed with initial primary lung cancer (IPLC) and SPLC via linkage to Surveillance, Epidemiology, and End Results registries. We estimated the 10-year cumulative incidence of IPLC (in the entire cohort) and SPLC (among IPLC patients). A standardized incidence ratio (SIR) was calculated as the ratio of SPLC-to-IPLC incidence by race and ethnicity., Results: Among 202 692 participants, 6788 (3.3%) developed IPLC over 3 871  417 person-years. The 10-year cumulative IPLC incidence was lower among Hispanics (0.80%, 0.72 to 0.88) vs Whites (1.67%, 1.56 to 1.78) or Blacks (2.44%, 2.28 to 2.60). However, the 10-year SPLC incidence following IPLC was higher among Hispanics (3.11%, 1.62 to 4.61) vs Whites (2.80%, 1.94 to 3.66) or Blacks (2.29%, 1.48 to 3.10), resulting in a significantly higher SIR for Hispanics (SIR = 8.27, 5.05 to 12.78) vs Whites (SIR = 5.60, 4.11 to 7.45) or Blacks (SIR = 3.48, 2.42 to 4.84; P < .001)., Conclusion: Hispanics have a higher SPLC incidence following IPLC than other races, which may be potentially due to better survival after IPLC and extended duration for SPLC development. Continuing surveillance is warranted to reduce racial disparities among LC survivors., (© The Author(s) 2024. Published by Oxford University Press.)

Competing Interests: Conflict of Interest: None declared.

Current guidelines recommend urine culture after catheter replacement to diagnose catheter-associated urinary tract infections (CA-UTI) in patients with long-term catheters, but it's unclear if this applies to short-term catheterizations. We studied 52 patients with catheters for less than 28 days, showing symptoms of CA-UTI. We collected urine from the catheter port initially and from the new catheter within 2 hours of replacement. Positive culture rates were 36.5 % before and 28.8 % after replacement. Significant differences in urine culture results were observed in 32.7 % of cases postreplacement (P = .0184), increasing to 78.9 % after excluding negative pre-replacement cultures (P = 0.0003). Duration of catheterization didn't affect urine bacteriology changes post-replacement. This suggests that urine bacteriology often differs after catheter replacement in short-term catheterizations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Rosuvastatin (RSV) is widely used to treat hyperlipidemia and hypercholesterolemia and is recommended for the primary and secondary prevention of cardiovascular diseases (CVD). In this study, we aimed to explore its action and mechanism in lung adenocarcinoma (LUAD) therapy. Lewis and CMT64 cell-based murine subcutaneous LUAD models were employed to explore the effects of RSV monotherapy combined with cisplatin and gemcitabine. Human lung fibroblasts and human LUAD cell lines were used to assess the effects of RSV on normal and LUAD cells. Bioinformatics and RNA interference were used to observe the contribution of cyclin A2 (CCNA2) knockdown to RSV inhibition and to improve chemosensitivity in LUAD. RSV significantly suppressed grafted tumor growth in a murine subcutaneous LUAD model and exhibited synergistic anti-tumor activity with cisplatin and gemcitabine. In vitro and in vivo experiments demonstrated that RSV impaired the proliferation and migration of cancer cells while showing little inhibition of normal lung cells. RNA interference and CCK8 detection preliminarily indicated that RSV inhibited tumor growth and enhanced the chemosensitivity to cisplatin and gemcitabine by downregulating CCNA2. RSV suppressed LUAD progression and enhanced chemosensitivity to cisplatin and gemcitabine by downregulating CCNA2, which should be prior consideration for the treatment of LUAD, especially for patients co-diagnosed with hyperlipidemia and hypercholesterolemia.

Background: Deoxyribonuclease 2 (DNase II) plays a key role in clearing cytoplasmic double-stranded DNA (dsDNA). Deficiency of DNase II leads to DNA accumulation in the cytoplasm. Persistent dsDNA in neurons is an early pathological hallmark of senescence and neurodegenerative diseases including Alzheimer's disease (AD). However, it is not clear how DNase II and neuronal cytoplasmic dsDNA influence neuropathogenesis. Tau hyperphosphorylation is a key factor for the pathogenesis of AD. The effect of DNase II and neuronal cytoplasmic dsDNA on neuronal tau hyperphosphorylation remains unclarified., Methods: The levels of neuronal DNase II and dsDNA in WT and Tau-P301S mice of different ages were measured by immunohistochemistry and immunolabeling, and the levels of DNase II in the plasma of AD patients were measured by ELISA. To investigate the impact of DNase II on tauopathy, the levels of phosphorylated tau, phosphokinase, phosphatase, synaptic proteins, gliosis and proinflammatory cytokines in the brains of neuronal DNase II-deficient WT mice, neuronal DNase II-deficient Tau-P301S mice and neuronal DNase II-overexpressing Tau-P301S mice were evaluated by immunolabeling, immunoblotting or ELISA. Cognitive performance was determined using the Morris water maze test, Y-maze test, novel object recognition test and open field test., Results: The levels of DNase II were significantly decreased in the brains and the plasma of AD patients. DNase II also decreased age-dependently in the neurons of WT and Tau-P301S mice, along with increased dsDNA accumulation in the cytoplasm. The DNA accumulation induced by neuronal DNase II deficiency drove tau phosphorylation by upregulating cyclin-dependent-like kinase-5 (CDK5) and calcium/calmodulin activated protein kinase II (CaMKII) and downregulating phosphatase protein phosphatase 2A (PP2A). Moreover, DNase II knockdown induced and significantly exacerbated neuron loss, neuroinflammation and cognitive deficits in WT and Tau-P301S mice, respectively, while overexpression of neuronal DNase II exhibited therapeutic benefits., Conclusions: DNase II deficiency and cytoplasmic dsDNA accumulation can initiate tau phosphorylation, suggesting DNase II as a potential therapeutic target for tau-associated disorders., (© 2024. The Author(s).)

Dengue is an arbovirus transmitted by the Aedes spp. mosquito. Approximately 390 million infections occur annually per World Health Organization estimates, with significant increases in infections throughout the last decade. The disease is endemic in warmer climates throughout the world, though cases may also be imported to non-endemic regions by returning travelers. Patients experience a wide variety of symptoms ranging from asymptomatic infection to severe disease requiring critical care. Emergency clinicians should consider the diagnosis of dengue in patients from endemic areas presenting with a flu-like illness, rash, and evidence of bleeding., Competing Interests: Declaration of competing interest MJP, BL, and SYL have no conflicts of interest to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The poor efficiency and low immunogenicity of photodynamic therapy (PDT), and the immunosuppressive tumor microenvironment (ITM) lead to tumor recurrence and metastasis. In this work, TCPP-T ER -Zn@RSV nanosheets (TZR NSs) that co-assembled from the endoplasmic reticulum (ER)-targeting photosensitizer TCPP-T ER -Zn nanosheets (TZ NSs for short) and the autophagy promoting and indoleamine-(2, 3)-dioxygenase (IDO) inhibitor-like resveratrol (RSV) are fabricated to enhance antitumor PDT. TZR NSs exhibit improved therapeutic efficiency and amplified immunogenic cancer cell death (ICD) by ER targeting PDT and ER autophagy promotion. TZR NSs reversed the ITM with an increase of CD8+ T cells and reduce of immunosuppressive Foxp3 regulatory T cells, which effectively burst antitumor immunity thus clearing residual tumor cells. The ER-targeting TZR NSs developed in this paper presents a simple but valuable reference for high-efficiency tumor photodynamic immunotherapy., (© 2024 Wiley‐VCH GmbH.)

To quantitatively evaluate the effect of the process parameters and the material properties on the temperature in laser powder bed fusion (LPBF), this paper proposed a sensitivity analysis of the temperature based on the validated prediction model. First, three different heat source modes-point heat source, Gaussian surface heat source, and Gaussian body heat source-were introduced. Then, a case study of Ti6Al4V is conducted to determine the suitable range of heat source density for the three different heat source models. Based on this, the effects of laser processing parameters and material thermophysical parameters on the temperature field and molten pool size are quantitatively discussed based on the Gaussian surface heat source. The results indicate that the Gaussian surface heat source and the Gaussian body heat source offer higher prediction accuracy for molten pool width compared to the point heat source under similar processing parameters. When the laser energy density is between 40 and 70 J/mm 3 , the prediction accuracy of the Gaussian surface heat source and the body heat source is similar, and the average prediction errors are 4.427% and 2.613%, respectively. When the laser energy density is between 70 and 90 J/mm 3 , the prediction accuracy of the Gaussian body heat source is superior to that of the Gaussian surface heat source. Among the influencing factors, laser power exerts the greatest influence on the temperature field and molten pool size, followed by scanning speed. In particular, laser power and scan speed contribute 38.9% and 23.5% to the width of the molten pool, 39.1% and 19.6% to the depth of the molten pool, and 38.9% and 21.5% to the maximum temperature, respectively.

This study uses real-time monitoring, at microsecond time scales, with a charge-sensing particle detector to investigate the evaporation and fission processes of methanol/micrometer-sized polystyrene beads (PS beads) droplets and bacterial particles droplets generated via electrospray ionization (ESI) under elevated temperatures. By incrementally raising capillary temperatures, the solvent, such as methanol on 0.75 μm PS beads, experiences partial evaporation. Further temperature increase induces fission, and methanol molecules continue to evaporate until PS ions are detected after this range. Similar partial evaporation is observed on 3 μm PS beads. However, the shorter period of the fission temperature range is necessary compared to 0.75 μm PS beads. For the spherical-shaped bacterium, Staphylococcus aureus , the desolvation process shows a similar fission period as compared to 0.75 μm PS beads. Comparably, the rod-shaped bacteria, Escherichia coli EC11303, and E. coli strain W have shorter fission periods than S. aureus . This research provides insights into the evaporation and fission mechanisms of ESI droplets containing different sizes and shapes of micrometer-sized particles, contributing to a better understanding of gaseous macroion formation.

(Basic awareness and understanding of antimicrobial resistance and prevailing mechanisms can aid emergency physicians in providing appropriate care to patients with infections due to a multidrug-resistant organism (MDRO). Empiric treatment of MDRO infections should be approached with caution and guided by the most likely pathogens based on differential diagnosis, severity of the illness, suspected source of infection, patient-specific factors, and local antibiotic susceptibility patterns. Newer broad-spectrum antibiotics should be reserved for critically ill patients where there is a high likelihood of infection with an MDRO.)., Competing Interests: Disclosure The authors report no conflicts of interest or funding relevant to the preparation of this article. SYL received support through the Foundation for Barnes-Jewish Hospital, United States and the Washington University Institute of Clinical and Translational Sciences which is, in part, supported by the NIH, United States/National Center for Advancing Translational Sciences (NCATS), Clinical and Translational Science Award (CTSA) program (UL1TR002345)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Salmonella , a zoonotic pathogen, significantly impacts global human health. Understanding its serotype distribution and antimicrobial resistance is crucial for effective control measures and medical interventions., Methods: We collected Salmonella isolates and demographic data from Taiwanese hospitals between 2004 and 2022, analyzing their serotypes and antimicrobial susceptibility., Results: Among 40,595 isolates, salmonellosis predominated in children aged 0-4 (61.2%) years and among males (55.2%). Males also showed higher rates of extraintestinal infections (18.1% vs 16.0%, P <0.001), particularly, in the ≥65 years age group (52.4%). The top five serovars were S. Enteritidis (32.8%), S. Typhimurium (21.7%), S. Newport (6.2%), S. Stanley (4.7%), and S. Anatum (4.0%). Notably, S . Enteritidis prevalence increased from 23.9% (2004-2005) to 43.6% (2021-2022). Antimicrobial resistance was high, with a 51.6% multidrug resistance (MDR) rate. Disturbingly, MDR rates exceeded 90% in serovars Albany, Schwarzengrund, Choleraesuis, and Goldcoast. Resistance to key therapeutic agents, azithromycin, cefotaxime, and ciprofloxacin, exhibited concerning upward trends, and the surge in cefotaxime and ciprofloxacin resistance was closely linked to the emergence and spread of MDR S. Anatum and S. Goldcoast clones., Conclusions: Prioritizing control measures against S . Enteritidis and closely monitoring the prevalence and spread of MDR clones are imperative to mitigate Salmonella infections in Taiwan., Competing Interests: The authors have no competing interests to declare., (© 2024 The Author(s).)

Background: We characterized age at diagnosis and estimated sex differences for lung cancer and its histological subtypes among individuals who never smoke., Methods: We analyzed the distribution of age at lung cancer diagnosis in 33,793 individuals across 8 cohort studies and two national registries from East Asia, the United States (US) and the United Kingdom (UK). Student's t-tests were used to assess the study population differences (Δ years) in age at diagnosis comparing females and males who never smoke across subgroups defined by race/ethnicity, geographic location, and histological subtypes., Results: We found that among Chinese individuals diagnosed with lung cancer who never smoke, females were diagnosed with lung cancer younger than males in the Taiwan Cancer Registry (n = 29,832) (Δ years = -2.2 (95% confidence interval (CI):-2.5, -1.9), in Shanghai (n = 1049) (Δ years = -1.6 (95% CI:-2.9, -0.3), and in Sutter Health and Kaiser Permanente Hawai'i in the US (n = 82) (Δ years = -11.3 (95% CI: -17.7, -4.9). While there was a suggestion of similar patterns in African American and non-Hispanic White individuals. the estimated differences were not consistent across studies and were not statistically significant., Conclusions: We found evidence of sex differences for age at lung cancer diagnosis among individuals who never smoke., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The elderly frequently present impaired blood-brain barrier which is closely associated with various neurodegenerative diseases. However, how the albumin, the most abundant protein in the plasma, leaking through the disrupted BBB, contributes to the neuropathology remains poorly understood. We here demonstrated that mouse serum albumin-activated microglia induced astrocytes to A1 phenotype to remarkably increase levels of Elovl1, an astrocytic synthase for very long-chain saturated fatty acids, significantly promoting VLSFAs secretion and causing neuronal lippoapoptosis through endoplasmic reticulum stress response pathway. Moreover, MSA-activated microglia triggered remarkable tau phosphorylation at multiple sites through NLRP3 inflammasome pathway. Intracerebroventricular injection of MSA into the brains of C57BL/6J mice to a similar concentration as in patient brains induced neuronal apoptosis, neuroinflammation, increased tau phosphorylation, and decreased the spatial learning and memory abilities, while Elovl1 knockdown significantly prevented the deleterious effect of MSA. Overall, our study here revealed that MSA induced tau phosphorylation and neuron apoptosis based on MSA-activated microglia and astrocytes, respectively, showing the critical roles of MSA in initiating the occurrence of tauopathies and cognitive decline, and providing potential therapeutic targets for MSA-induced neuropathology in multiple neurodegenerative disorders., (© 2024. The Author(s).)

The neurotoxic α-synuclein (α-syn) oligomers play an important role in the occurrence and development of Parkinson's disease (PD), but the factors affecting α-syn generation and neurotoxicity remain unclear. We here first found that thrombomodulin (TM) significantly decreased in the plasma of PD patients and brains of A53T α-syn mice, and the increased TM in primary neurons reduced α-syn generation by inhibiting transcription factor p-c-jun production through Erk1/2 signaling pathway. Moreover, TM decreased α-syn neurotoxicity by reducing the levels of oxidative stress and inhibiting PAR1-p53-Bax signaling pathway. In contrast, TM downregulation increased the expression and neurotoxicity of α-syn in primary neurons. When TM plasmids were specifically delivered to neurons in the brains of A53T α-syn mice by adeno-associated virus (AAV), TM significantly reduced α-syn expression and deposition, and ameliorated the neuronal apoptosis, oxidative stress, gliosis and motor deficits in the mouse models, whereas TM knockdown exacerbated these neuropathology and motor dysfunction. Our present findings demonstrate that TM plays a neuroprotective role in PD pathology and symptoms, and it could be a novel therapeutic target in efforts to combat PD. Schematic representation of signaling pathways of TM involved in the expression and neurotoxicity of α-syn. A TM decreased RAGE, and resulting in the lowered production of p-Erk1/2 and p-c-Jun, and finally reduce α-syn generation. α-syn oligomers which formed from monomers increase the expression of p-p38, p53, C-caspase9, C-caspase3 and Bax, decrease the level of Bcl-2, cause mitochondrial damage and lead to oxidative stress, thus inducing neuronal apoptosis. TM can reduce intracellular oxidative stress and inhibit p53-Bax signaling by activating APC and PAR-1. B The binding of α-syn oligomers to TLR4 may induce the expression of IL-1β, which is subsequently secreted into the extracellular space. This secreted IL-1β then binds to its receptor, prompting p65 to translocate from the cytoplasm into the nucleus. This translocation downregulates the expression of KLF2, ultimately leading to the suppression of TM expression. By Figdraw., (© 2024. The Author(s).)

Background: Gastric adenocarcinoma (GAC) is often diagnosed at advanced stages and portends a poor prognosis. We hypothesized that electronic health records (EHR) could be leveraged to identify individuals at highest risk for GAC from the population seeking routine care., Methods: This was a retrospective cohort study, with endpoint of GAC incidence as ascertained through linkage to an institutional tumor registry. We utilized 2010 to 2020 data from the Palo Alto Medical Foundation, a large multispecialty practice serving Northern California. The analytic cohort comprised individuals ages 40-75 receiving regular ambulatory care. Variables collected included demographic, medical, pharmaceutical, social, and familial data. Electronic phenotyping was based on rule-based methods., Results: The cohort comprised 316,044 individuals and approximately 2 million person-years (p-y) of observation. 157 incident GACs occurred (incidence 7.9 per 100,000 p-y), of which 102 were non-cardia GACs (incidence 5.1 per 100,000 p-y). In multivariable analysis, male sex [HR: 2.2, 95% confidence interval (CI): 1.6-3.1], older age, Asian race (HR: 2.5, 95% CI: 1.7-3.7), Hispanic ethnicity (HR: 1.9, 95% CI: 1.1-3.3), atrophic gastritis (HR: 4.6, 95% CI: 2.2-9.3), and anemia (HR: 1.9, 95% CI: 1.3-2.6) were associated with GAC risk; use of NSAID was inversely associated (HR: 0.3, 95% CI: 0.2-0.5). Older age, Asian race, Hispanic ethnicity, atrophic gastritis, and anemia were associated with non-cardia GAC., Conclusions: Routine EHR data can stratify the general population for GAC risk., Impact: Such methods may help triage populations for targeted screening efforts, such as upper endoscopy., (©2024 American Association for Cancer Research.)

Importance: Amblyopia can result in permanent vision loss if not properly treated before age 7 years. In 2017, the US Preventive Services Task Force recommended that vision screening should occur at least once in all children aged 3 to 5 years to detect amblyopia., Objective: To understand trends and factors associated with screening, referral, or diagnosis of amblyopia before and after photoscreening expansion across a relatively large health care system in late 2017., Design, Setting, and Participants: This is a retrospective cohort study of electronic health record data from patients with a well child care visit at approximately age 3 years (ages 2.75-3.25 years) in a relatively large, multispecialty group practice in Northern California and linked census data between 2015 and 2022. Data were extracted and analyzed from October 2022 through August 2023., Exposures: Patient sex, race and ethnicity, immunization records, previous well child care visits, and census-level median household income., Main Outcomes and Measures: Vision screening, pediatric ophthalmology referral, or amblyopia diagnosis, compared using adjusted odds ratios (AORs)., Results: The study included 2015-2017 data from 23 246 patients aged 3 years with at least 1 well child care visit (11 206 [48.2%] female) compared with 2018-2022 postexpansion data from 34 281 patients (16 517 [48.2%] female). The screening rate increased from 5.7% (424 of 7505) in 2015 to 72.1% (4578 of 6354) in 2022. The referral rate increased from 17.0% (1279 of 7505) in 2015 to 23.6% (1836 of 7792) in 2018. The diagnosis rate was 2.7% (200 of 7505) in 2015, peaked at 3.4% (263 of 7792) in 2018, and decreased to 1.4% (88 of 6354) in 2022. Compared with White patients, patients who were Asian, Black, or Hispanic were less likely to be screened (Asian: AOR, 0.80; 95% CI, 0.72-0.88; Black: AOR, 0.71; 95% CI, 0.53-0.96; Hispanic: AOR, 0.88; 95% CI, 0.80-0.97). Compared with White patients, patients who were Asian or Hispanic were more likely to be referred (Asian: AOR, 1.49; 95% CI, 1.36-1.62; Hispanic: AOR, 1.32; 95% CI, 1.18-1.48) and were more likely to be diagnosed (Asian: AOR, 1.29; 95% CI, 1.07-1.56; Hispanic: AOR, 1.67; 95% CI, 1.33-2.11)., Conclusions and Relevance: In this study, increased availability of photoscreeners was associated with an increase in overall rates of vision screening for children aged 3 years in a relatively large health care system. Given that US rates of visual impairment are predicted to increase, additional targeted interventions would be needed to address remaining disparities in amblyopia care along patient- and clinician-level factors.

Introduction: Adenoma detection rate (ADR) is an accepted benchmark for screening colonoscopy. Factors driving ADR and its relationship with sessile serrated lesions detection rate (SSLDR) over time remain unclear. We aim to explore patient, physician, and procedural influences on ADR and SSLDR trends., Methods: Using a large healthcare system in northern California from January 2010 to December 2020, a total of 146,818 screening colonoscopies performed by 33 endoscopists were included. ADR and SSLDR were calculated over time using natural language processing. Logistic regression was used to calculate the odd ratios of patient demographics, physician attributes, and procedural details over time., Results: Between 2010 and 2020, ADR rose from 19.4% to 44.4%, whereas SSLDR increased from 1.6% to 11.6%. ADR increased by 2.7% per year (95% confidence interval 1.9%-3.4%), and SSLDR increased by 1.0% per year (95% confidence interval 0.8%-1.2%). Higher ADR was associated with older age, male sex, higher body mass index, current smoker, higher comorbidities, and high-risk colonoscopy. By contrast, SSLDR was associated with younger age, female sex, white race, and fewer comorbidities. Patient and procedure characteristics did not significantly change over time ( P -interaction >0.05). Longer years in practice and male physician were associated with lower ADR and SSLDR in 2010, but significantly attenuated over time ( P -interaction <0.05)., Discussion: Both ADR and SSLDR have increased over time. Patient and procedure factors did not significantly change over time. Male endoscopist and longer years in practice had lower initial ADR and SSLDR, but significantly lessened over time., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: Malaria is a potentially fatal parasitic disease transmitted by the Anopheles mosquito. A resurgence in locally acquired infections has been reported in the U.S., Objective: This narrative review provides a focused overview of malaria for the emergency clinician, including the epidemiology, presentation, diagnosis, and management of the disease., Discussion: Malaria is caused by Plasmodium and is transmitted by the Anopheles mosquito. Disease severity can range from mild to severe. Malaria should be considered in any returning traveler from an endemic region, as well as those with unexplained cyclical, paroxysms of symptoms or unexplained fever. Patients most commonly present with fever and rigors but may also experience cough, myalgias, abdominal pain, fatigue, vomiting, and diarrhea. Hepatomegaly, splenomegaly, pallor, and jaundice are findings associated with malaria. Although less common, severe malaria is precipitated by microvascular obstruction with complications of anemia, acidosis, hypoglycemia, multiorgan failure, and cerebral malaria. Peripheral blood smears remain the gold standard for diagnosis, but rapid diagnostic tests are available. Treatment includes specialist consultation and antimalarial drugs tailored depending on chloroquine resistance, geographic region of travel, and patient comorbidities. Supportive care may be required, and patients with severe malaria will require resuscitation. Most patients will require admission for treatment and further monitoring., Conclusion: Emergency medicine clinicians should be aware of the presentation, diagnosis, evaluation, and management of malaria to ensure optimal outcomes., Competing Interests: Declaration of Competing Interest None. None of the authors have submitted a review on this topic or published previously on this topic. This manuscript did not use AI for its construction., (Published by Elsevier Inc.)

As a potential treatment strategy for low immunogenic triple negative breast cancer (TNBC), photodynamic therapy (PDT) induced antitumor immunotherapy is greatly limited by the immunosuppressive tumor microenvironment (ITM), especially the M2 phenotype tumor-associated macrophages (TAMs). The balance of arginine metabolism plays an important role in TAMs polarization. Herein, a multifunctional nanoplatform (defined as HN-HFPA) was employed to burst the anti-tumor immunity of TNBC post PDT by reeducating TAMs through interfering the TAMs-associated arginine metabolism. The L-arginine (L-Arg) was loaded in the hollow cavity of HN-HFPA, which could not only generate nitric oxide (NO) for tumor therapy, but also serve as a substrate of arginine metabolism pathway. As an inhibitor of arginases-1 (Arg-1) of M2 TAMs, L-norvaline (L-Nor) was modified to the hyaluronic acid (HA), and coated in the surface of HFPA. After degradation of HA by hyaluronidase in tumor tissue and GSH-mediated disintegration, HN-HFPA depleted intracellular GSH, produced remarkable reactive oxygen species (ROS) under light irradiation and released L-Arg to generate NO, which induced tumor immunogenic cell death (ICD). Real-time ultrasound imaging of tumor was realized taking advantage of the gas feature of NO. The L-Nor suppressed the Arg-1 overexpressed in M2, which skewed the balance of arginine metabolism and reversed the ITM with increased ratios of M1 and CD8 + T cells, finally resulted in amplified antitumor immune response and apparent tumor metastasis inhibition. This study remodeled ITM to strengthen immune response post PDT, which provided a promising treatment strategy for TNBC., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Presented herein is a palladium-catalyzed asymmetric (3 + 2) annulation reaction between 1,3-dienes and 2-formylarylboronic acids, proceeding in a cascade vinylogous addition and Suzuki coupling process. Both electron-neutral and electron-deficient 1,3-dienes are compatible under similar catalytic conditions, and distinct regioselectivity is observed via functional-group control of 1,3-diene substrates. A collection of 1-indanols with dense functionalities is constructed stereoselectively.

Introduction: Nightclubs are entertainment and hospitality venues historically vulnerable to terrorist attacks. This study identified and characterized terrorist attacks targeting nightclubs and discotheques documented in the Global Terrorism Database (GTD) over a 50-y period., Methods: A search of the Global Terrorism Database (GTD) was conducted from 1970 to 2019. Precoded variables for target type "business" and target subtype "entertainment/cultural/stadium/casino" were used to identify attacks potentially involving nightclubs. Nightclub venues were specifically identified using the search terms "club," "nightclub," and "discotheque." Two authors manually reviewed each entry to confirm the appropriateness for inclusion. Descriptive statistics were performed using R (3.6.1)., Results: A total of 114 terrorist attacks targeting nightclub venues were identified from January 1, 1970, through December 31, 2019. Seventy-four (64.9%) attacks involved nightclubs, while forty (35.1%) attacks involved discotheques. A bombing or explosion was involved in 84 (73.7%) attacks, followed by armed assault in 14 (12.3%) attacks. The highest number of attacks occurred in Western Europe and Sub-Saharan Africa. In total, 284 persons died, and 1175 persons were wounded in attacks against nightclub venues., Conclusions: While terrorist attacks against nightclub venues are infrequent, the risk for mass casualties and injuries can be significant, mainly when explosives and armed assaults are used.

Motivation: Providing a dynamic assessment of prognosis is essential for improved personalized medicine. The landmark model for survival data provides a potentially powerful solution to the dynamic prediction of disease progression. However, a general framework and a flexible implementation of the model that incorporates various outcomes, such as competing events, have been lacking. We present an R package, dynamicLM, a user-friendly tool for the landmark model for the dynamic prediction of survival data under competing risks, which includes various functions for data preparation, model development, prediction and evaluation of predictive performance., Implementation: dynamicLM as an R package., General Features: The package includes options for incorporating time-varying covariates, capturing time-dependent effects of predictors and fitting a cause-specific landmark model for time-to-event data with or without competing risks. Tools for evaluating the prediction performance include time-dependent area under the ROC curve, Brier Score and calibration., Availability: Available on GitHub [https://github.com/thehanlab/dynamicLM]., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Objectives: We investigated the temporal trends of Salmonella enterica serovar Typhimurium (S. Typhimurium) clones in Taiwan from 2004 to 2019, focusing on antimicrobial resistance (AMR), resistance genetic determinants, and plasmid types., Methods: Salmonella isolates were characterized using pulsed-field gel electrophoresis (PFGE), whole-genome sequencing, and antimicrobial susceptibility testing. Clones were defined using PFGE clustering and the hierarchical cgMLST clustering (HierCC) assignments., Results: Seven major S. Typhimurium clones, HC100&#95;2, 13, 41, 305, 310, 501, and 46261, accounted for 97.6% (8079/8275) of human isolates in Taiwan. Each clone displayed a unique AMR profile, resistance genetic determinants, and plasmid types. Four highly resistant clones (HC100&#95;2, 41, 305, and 310) exhibited multiple resistance in 86.5% to 96.1% of isolates. HC100&#95;305 and HC100&#95;2 were pandemic multidrug-resistant clones, characterized by resistance to ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline (ACSSuT) and ASSuT, respectively. The prevalence of the ACSSuT clone decreased from 68.7% of S. Typhimurium isolates in 2004 to 1.7% in 2019, while the ASSuT clone emerged in 2007 and became the largest clone after 2010. Several plasmids, including IncHI2-IncHI2A, IncC, IncFIB(K), and IncI1-1(α), carried multiple resistance genes or were associated with the carriage of mph(A), bla CMY-2 , and bla DHA-1 ., Conclusions: Between 2004 and 2019, Taiwan experienced the emergence, prevalence, and subsequent decline of several highly resistant S. Typhimurium clones. The clones defined using the HierCC approach have global comparability. The increasing resistance to third-generation cephalosporins, cephamycins, ciprofloxacin, and azithromycin in recent years poses a significant medical concern., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Lynch syndrome (LS) is the most common cause of inherited colorectal cancer (CRC). Universal tumor screening (UTS) of newly diagnosed CRC cases is recommended to aid in diagnosis of LS and reduce cancer-related morbidity and mortality. However, not all health systems have adopted UTS processes and implementation may be inconsistent due to system and patient-level complexities., Methods: To identify barriers, facilitators, and suggestions for improvements of the UTS process from the patient perspective, we conducted in-depth, semi-structured interviews with patients recently diagnosed with CRC, but not screened for or aware of LS. Patients were recruited from eight regionally diverse US health systems. Interviews were conducted by telephone, 60-minutes, audio-recorded, and transcribed. An inductive, constant comparative analysis approach was employed.  RESULTS: We completed 75 interviews across the eight systems. Most participants were white (79%), about half (52%) were men, and the mean age was 60 years. Most self-reported either no (60%) or minimal (40%) prior awareness of LS. Overall, 96% of patients stated UTS should be a routine standard of care for CRC tumors, consistently citing four primary motivations for wanting to know their LS status and engage in the process for LS identification: "knowledge is power"; "family knowledge"; "prevention and detection"; and "treatment and surveillance." Common concerns pertaining to the process of screening for and identifying LS included: creating anticipatory worry for patients, the potential cost and the accuracy of the genetic test, and possibly having one's health insurance coverage impacted by the LS diagnosis. Patients suggested health systems communicate LS results in-person or by phone from a trained expert in LS; offer proactive verbal and written education about LS, the screening steps, and any follow-up surveillance recommendations; and support patients in communicating their LS screening to any of their blood relatives., Conclusion: Our qualitative findings demonstrate patients with CRC have a strong desire for healthcare systems to regularly implement and offer UTS. Patients offer key insights for health systems to guide future implementation and optimization of UTS and other LS screening programs and maximize diagnosis of individuals with LS and improve cancer-related surveillance and outcomes., Trial Registration: Not available: not a clinical trial., (© 2023. The Author(s).)

The marked increase in the incidence rate of brucellosis is a serious public health concern in Jiangsu Province. However, its temporal and spatial distribution has not been studied in depth. The main purpose of this study is to depict the demographic, temporal and spatial distribution patterns and clustering characteristics of brucellosis cases in Jiangsu Province, China, from 2006 to 2021 to develop and implement effective scientific prevention and control strategies. Data for human brucellosis cases in Jiangsu Province from 2006 to 2021 were obtained from the Nationwide Notifiable Infectious Diseases Reporting Information System (NIDRIS). Spatial autocorrelation analysis and temporal-spatial scan statistics were used to identify potential changes in the spatial and temporal distributions of human brucellosis in Jiangsu Province. During the years 2006-2021, 1347 brucellosis cases were reported in Jiangsu Province, with an average annual incidence rate of 0.1036 per 100,000 individuals. Middle-aged and elderly individuals (aged 40-69 years) were the main infected populations, accounting for 69.72% (939/1347) of all reported cases. The incidence of brucellosis in Jiangsu showed a long-term increasing trend and displayed pronounced seasonal variations, with the peak occurring between April and June annually. The incidence gradually expanded from the northern and southern areas to the central areas between 2006 and 2021. Global spatial autocorrelation analysis demonstrated a positive correlation in the incidence of brucellosis between 2008 and 2012-2021. Temporal-spatial clustering analysis showed that the primary cluster was detected in the northern, highly endemic regions of Jiangsu, and the three secondary clusters were in areas where there had been outbreaks of brucellosis. Human brucellosis remains a serious public health issue in Jiangsu Province. Northern and southern Jiangsu regions, with high rates of brucellosis, may require special plans and measures to monitor and control the disease. Additionally, the capacity to respond to outbreaks in high-incidence areas should be improved to prevent further brucellosis outbreaks., (© 2023. The Author(s).)

The use of non-pharmacological strategies to complement pharmacological approaches can enhance cancer pain management by promoting patient autonomy and increasing management effectiveness. This study aimed to explore the required behavioral adaptations and situational barriers that cancer patients encounter when utilizing non-pharmacological strategies to manage pain. We adopted an exploratory-descriptive qualitative research approach, purposive sampling, and semi-structured interview guidelines to conduct face-to-face interviews with 18 cancer patients experiencing moderate or severe levels of worst pain. Data were analyzed using inductive content analysis to explore patients' experiences. Five themes described the behavioral adaptations of patients using non-pharmacological strategies to deal with cancer pain: finding complementary therapies, utilizing assistive skills, adapting to assistive skills, diverting attention, and seeking help. Situational barriers faced by patients include being in the workplace or in a climate-affected environment. Behavioral adaptation is necessary for non-pharmacological strategies to coping with cancer pain. The behavioral skills can help the patients to overcome situational barriers to engagement with these strategies. Thus, health professionals are expected to help the patients acquire adequate behavioral adaptation and skills for self-pain management, and assess the effectiveness of the strategies.

Importance: Lung cancer among never-smokers accounts for 25% of all lung cancers in the US; recent therapeutic advances have improved survival among patients with initial primary lung cancer (IPLC), who are now at high risk of developing second primary lung cancer (SPLC). As smoking rates continue to decline in the US, it is critical to examine more closely the epidemiology of lung cancer among patients who never smoked, including their risk for SPLC., Objective: To estimate and compare the cumulative SPLC incidence among lung cancer survivors who have never smoked vs those who have ever smoked., Design, Setting, and Participants: This population-based prospective cohort study used data from the Multiethnic Cohort Study (MEC), which enrolled participants between April 18, 1993, and December 31, 1996, with follow-up through July 1, 2017. Eligible individuals for this study were aged 45 to 75 years and had complete smoking data at baseline. These participants were followed up for IPLC and further SPLC development through the Surveillance, Epidemiology, and End Results registry. The data were analyzed from July 1, 2022, to January 31, 2023., Exposures: Never-smoking vs ever-smoking exposure at MEC enrollment., Main Outcomes and Measures: The study had 2 primary outcomes: (1) 10-year cumulative incidence of IPLC in the entire study cohort and 10-year cumulative incidence of SPLC among patients with IPLC and (2) standardized incidence ratio (SIR) (calculated as the SPLC incidence divided by the IPLC incidence) by smoking history., Results: Among 211 414 MEC participants, 7161 (3.96%) developed IPLC over 4 038 007 person-years, and 163 (2.28%) developed SPLC over 16 470 person-years. Of the participants with IPLC, the mean (SD) age at cohort enrollment was 63.6 (7.7) years, 4031 (56.3%) were male, and 3131 (43.7%) were female. The 10-year cumulative IPLC incidence was 2.40% (95% CI, 2.31%-2.49%) among ever-smokers, which was 7 times higher than never-smokers (0.34%; 95% CI, 0.30%-0.37%). However, the 10-year cumulative SPLC incidence following IPLC was as high among never-smokers (2.84%; 95% CI, 1.50%-4.18%) as ever-smokers (2.72%; 95% CI, 2.24%-3.20%), which led to a substantially higher SIR for never-smokers (14.50; 95% CI, 8.73-22.65) vs ever-smokers (3.50; 95% CI, 2.95-4.12)., Conclusions and Relevance: The findings indicate that SPLC risk among lung cancer survivors who never smoked is as high as among those with IPLC who ever-smoked, highlighting the need to identify risk factors for SPLC among patients who never smoked and to develop a targeted surveillance strategy.

This study aimed to explore the role and mechanism of felodipine in lung cancer therapy. Murine subcutaneous lung squamous cancer (LUSC) models constructed by KLN-205 cells were utilized to assess the effect of felodipine monotherapy and in combination with the programmed cell death protein 1 antibody (PD1ab) and cytotoxic T lymphocyte-associated antigen-4 (CTLA4ab). Immunohistochemistry analysis was subsequently applied to detect the number of CD8+ T cells and Ki67+ cells. Lastly, a series of in vitro and in vivo experiments were performed to evaluate the effects of felodipine on human LUSC cells and explore the preliminary mechanism underlying felodipine inhibition. The results revealed that felodipine monotherapy exerted a significant inhibitory effect on LUSC growth and synergistic antitumoral activity with PD1ab and CTLA4ab. Meanwhile, immunohistochemistry analysis displayed that felodipine promoted CD8+ T-cell infiltration and downregulated Ki67 expression in tumor cells. Moreover, in vitro and in vivo experiments utilizing human LUSC cells determined that felodipine impaired the proliferative and migratory abilities of cancer cells. In addition, TCGA data analysis uncovered that nuclear factor of activated T cell (NFAT1) expression was positively correlated with overall survival and disease-free survival. Finally, the cell counting kit-8 assay signaled that felodipine might suppress tumor growth by modulating NFAT1., Competing Interests: Conflict of interest: Authors declare that they have no competing interest., (© 2023 the author(s), published by De Gruyter.)

Objectives: We sought to develop an evidence-based tool to risk stratify patients diagnosed with seasonal influenza in the emergency department (ED)., Methods: We performed a single-center retrospective cohort study of all adult patients diagnosed with influenza in a large tertiary care ED between 2008 and 2018. We evaluated demographics, triage vital signs, chest x-ray and laboratory results obtained in the ED. We used univariate and multivariate statistics to examine the composite primary outcome of death or need for intubation. We validated our findings in patients diagnosed between 2018 and 2020., Results: We collected data from 3128 subjects; 2196 in the derivation cohort and 932 in the validation cohort. Medical comorbidities, multifocal opacities or pleural effusion on chest radiography, older age, elevated respiratory rate, hypoxia, elevated blood urea nitrogen, blood glucose, blood lactate, and red blood cell distribution width were factors associated with intubation or death. We developed the Predicting Intubation in seasonal Influenza Patients diagnosed in the ED (PIIPED) risk-stratification tool from these factors. The PIIPED tool predicted intubation or death with an area under the receiver operating characteristic curve (AUC) of 0.899 in the derivation cohort and 0.895 in the validation cohort. A version of the tool including only factors available at ED triage, before laboratory or radiographic evaluation, exhibited AUC of 0.852 in the derivation cohort and 0.823 in the validation cohort., Conclusion: Clinical findings during an ED visit predict severe outcomes in patients with seasonal influenza. The PIIPED risk stratification tool shows promise but requires prospective validation., Competing Interests: The authors declare no financial conflicts related to this work., (© 2023 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)